Longitudinal Microbiome Composition and Stability Correlate with Increased Weight and Length of Very-Low-Birth-Weight Infants

Abstract

The microbiomes of 83 preterm very-low-birth-weight (VLBW) infants and clinical covariates were analyzed weekly over the course of their initial neonatal intensive care unit (NICU) stay, with infant growth as the primary clinical outcome. Birth weight significantly correlated with increased rate of weight gain in the first 6 weeks of life, while no significant relationship was observed between rate of weight gain and feeding type. Microbial diversity increased with age and was significantly correlated with weight gain and percentage of the mother’s own milk. As expected, infants who received antibiotics during their NICU stay had significantly lower alpha diversity than those who did not. Of those in the cohort, 25 were followed into childhood. Alpha diversity significantly increased between NICU discharge and age 2 years and between age 2 years and age 4 years, but the microbial alpha diversity of 4-year-old children was not significantly different from that of mothers. Infants who showed improved length over the course of their NICU stay had significantly more volatile microbial beta diversity results than and a significantly decreased microbial maturity index compared with infants who did not; interestingly, all infants who showed improved length during the NICU stay were delivered by Caesarean section. Microbial beta diversity results were significantly different between the time of the NICU stay and all other time points (for children who were 2 or 4 years old and mothers when their children were 2 or 4 years old). IMPORTANCE Preterm infants are at greater risk of microbial insult than full-term infants, including reduced exposure to maternal vaginal and enteric microbes, higher rates of formula feeding, invasive procedures, and administration of antibiotics and medications that alter gastrointestinal pH. This investigation of the VLBW infant microbiome over the course of the neonatal intensive care unit (NICU) stay, and at ages 2 and 4 years, showed that the only clinical variables associated with significant differences in taxon abundance were weight gain during NICU stay (Klebsiella and Staphylococcus) and antibiotic administration (Streptococcus and Bifidobacterium). At 2 and 4 years of age, the microbiota of these VLBW infants became similar to the mothers’ microbiota. The number of microbial taxa shared between the infant or toddler and the mother varied, with least the overlap between infants and mothers. Overall, there was a significant association between the diversity and structure of the microbial community and infant weight and length gain in an at-risk childhood population.

Gut and Lung Microbiota in Preterm Infants: Immunological Modulation and Implication in Neonatal Outcomes

“…The study results of Yee et al (55), complement previous data, showing an abundance of Proteobacteria in the preterm infants' microbiome (56,57). These authors described a negative correlation between infant weight gain during hospitalization and the relative abundances of Klebsiella and Staphylococcus.…”

The Gut Microbial Diversity of Newly Diagnosed Diabetics but Not of Prediabetics Is Significantly Different from That of Healthy Nondiabetics

“…The top 30 most abundant genera present in all samples and serum metabolites were included for analysis. The ranking of genera and serum metabolites according to mean decrease in accuracy (mean decrease Gini score) were obtained from the random forest algorithm using default parameters in the R 3.4.0. environment "randomForest" (with ntree ϭ 1,000), as mentioned in previous reports (67,68).…”

Annual Research Review: Critical windows – the microbiota–gut–brain axis in neurocognitive development

“…Note that, compared to the brain, the microbiota exhibits a relatively high level of ongoing plasticity beyond the developmental period [Colour figure can be viewed at wileyonlinelibrary.com] to external influences during development. The postnatal microbiota is relatively volatile, gaining stability across maturation (Koenig et al, 2011;Stewart et al, 2018;Yee et al, 2019), perhaps due to the increasing diversity described above in the section on Development of the microbiota. Periods of microbiota instability also occur during later phases of development, with a clear shift at weaning and an understudied transition considered likely during the adolescent period ( Figure 2).…”